Overview
The 5-HIAA (5-Hydroxyindoleacetic Acid) test is an important laboratory investigation used to detect and monitor a group of uncommon tumors known as carcinoid tumors. These tumors can produce excessive amounts of serotonin, a chemical involved in digestion and several regulatory body functions. When serotonin is broken down in the body, it forms 5-HIAA, which is then excreted in the urine.
By measuring urinary 5-HIAA, clinicians can assess whether serotonin production is abnormally high. This test is most often used when symptoms suggest carcinoid syndrome and to follow known cases over time.
What is 5-HIAA?
5-HIAA (5-Hydroxyindoleacetic Acid) is the main metabolic end product of serotonin. Serotonin itself plays roles in gastrointestinal activity, vascular tone, and several regulatory processes throughout the body.
In routine clinical practice, the 5-HIAA test is primarily associated with the evaluation of serotonin-secreting carcinoid tumors, which are most commonly located in the gastrointestinal tract or, less frequently, in the lungs. Excess serotonin production by these tumors leads to increased urinary excretion of 5-HIAA, which can be measured reliably in a 24-hour urine sample.
Where is 5-HIAA Produced in the Body?
Serotonin production:
Serotonin is produced mainly by enterochromaffin cells in the lining of the gastrointestinal tract. Smaller amounts are produced in other tissues, including parts of the nervous system.
Conversion to 5-HIAA:
After serotonin has exerted its biological effects, it is transported to the liver, where it is metabolized into 5-HIAA.
Excretion:
5-HIAA is then eliminated from the body through the kidneys into the urine. For this reason, urine measurement provides a practical and accurate reflection of overall serotonin metabolism.
Main Functions and Importance of the 5-HIAA Test
Clinically, the 5-HIAA test is used as a supportive diagnostic and monitoring tool rather than a general screening test.
It is particularly helpful in identifying carcinoid syndrome, a condition caused by sustained serotonin overproduction. In patients with known carcinoid tumors, repeated measurements help assess disease activity over time.
The test is also useful when patients present with symptoms such as recurrent flushing or unexplained diarrhea, where hormonal causes are being considered. In these situations, 5-HIAA assists clinicians in distinguishing serotonin-mediated conditions from more common gastrointestinal or allergic disorders.
Causes of Low 5-HIAA Levels
Low or normal urinary 5-HIAA levels usually reflect normal serotonin metabolism.
This is the expected finding in healthy individuals and in people without serotonin-producing tumors. Certain medications may also influence serotonin breakdown and result in lower measured levels, though this is usually of limited clinical significance.
Symptoms of Low 5-HIAA Levels
Low 5-HIAA levels themselves do not cause symptoms.
In most cases, they simply indicate the absence of excessive serotonin production. Symptoms related to serotonin deficiency are uncommon in the clinical context in which this test is used.
Causes of High 5-HIAA Levels
Persistently elevated 5-HIAA levels suggest increased serotonin production.
The most common cause is a carcinoid tumor, particularly those originating in the small intestine, appendix, colon, or bronchial system. Other rare neuroendocrine tumors may also increase serotonin output.
Temporary elevations can occur due to dietary influences or certain medications if present before or during sample collection. For this reason, clinicians interpret results carefully and often repeat testing if results are borderline or unexpected.
Symptoms of High 5-HIAA Levels (Carcinoid Syndrome)
High 5-HIAA levels do not cause symptoms directly. Instead, symptoms arise from excessive serotonin activity in the body.
Patients with carcinoid syndrome may experience episodic skin flushing, chronic diarrhea, abdominal discomfort, wheezing, or palpitations. These symptoms often fluctuate and may be triggered by stress or meals. Their pattern and persistence usually guide further investigation.
Reference Ranges for 5-HIAA Test
The test is most commonly performed using a 24-hour urine collection, which captures total daily excretion.
Typical reference interpretation includes:
- Values within the normal range suggest normal serotonin metabolism
- Mild elevations may require repeat testing or correlation with diet and medications
- Markedly elevated levels are strongly suggestive of serotonin-producing neuroendocrine tumors
Laboratory-specific reference intervals should always be used for final interpretation.
Sample Type and Test Method
- Sample type: 24-hour urine collection
- Alternative: Plasma 5-HIAA testing in selected situations
- Collection container: Special preservative-containing container
- Method: High-specificity techniques such as liquid chromatography or mass spectrometry
Proper sample handling is essential for accurate measurement.
Test Preparation
Accurate results depend on careful preparation and collection.
Certain foods naturally rich in serotonin can influence test results if consumed before or during collection. Similarly, some medications may interfere with measurement. For this reason, clinicians usually provide specific instructions tailored to the patient’s situation.
The 24-hour urine collection must include all urine passed during the designated period and should be handled exactly as instructed by the laboratory.
When to Consult a Doctor
Medical consultation is advised if a person experiences persistent flushing, unexplained diarrhea, wheezing, or recurrent abdominal discomfort without an obvious cause.
If test results show elevated 5-HIAA levels, further evaluation is often required to identify the source. This may include imaging studies or additional hormonal testing, depending on the clinical context.
Important Word Explanations
- Serotonin: A chemical messenger involved in digestion, vascular tone, and regulatory functions
- Metabolite: A substance formed when the body breaks down another compound
- Carcinoid Tumor: A slow-growing neuroendocrine tumor that may secrete serotonin
- Neuroendocrine Tumor: A tumor arising from hormone-producing nerve cells
- Flushing: Sudden redness and warmth of the skin due to hormonal effects
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